Optical contrast in optical imaging can be based on a variety of mechanisms: absorption, fluorescence, Raman spectra, scattering properties, and mechanical movement. Blood offers a strong absorber for detection of pathology characterized by altered blood perfusion and/or oxygen utilization. Fluorescence and Raman spectra offer contrast on the basis of chemical composition. Staining, fluorescent tags, and fluorescent protein expression offer another approach toward using fluorescence to characterize cells/tissues. Motion can be a contrast mechanism, as in laser doppler detection of blood flow or interferometric imaging of vibration. My laboratory has concentrated on using scattering as a contrast agent. Scattering provides a label-free mechanism of contrast, and hence is especially attractive for clinical use. After introducing the various contrast mechanisms, the talk will discuss (1) a non-invasive confocal reflectance method for characterizing the nanoarchitecture of tissues, (2) a spectroscopic method of characterizing the size distribution of tissue nanoarchiteture, and (3) a noninvasive interferometric method for characterizing the structural status of the nucleus.